Nakamura Kohei, Aimono Eriko, Oba Junna, Hayashi Hideyuki, Tanishima Shigeki, Hayashida Tetsu, Chiyoda Tatsuyuki, Kosaka Takeo, Hishida Tomoyuki, Kawakubo Hirohumi, Kitago Minoru, Okabayashi Koji, Funakoshi Takeru, Okita Hajime, Ikeda Sadakatsu, Takaishi Hiromasa, Nishihara Hiroshi
Genomics Unit, Keio Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo, 160-8582, Japan.
Department of Biomedical Informatics, Kansai Division, Mitsubishi Space Software Co., Ltd, Tokyo, Japan.
Med Oncol. 2021 Mar 12;38(4):36. doi: 10.1007/s12032-021-01482-1.
Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as "equivocal", which means that some ERBB2 amplification cases diagnosed as "HER2 negative" might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.
评估乳腺癌和胃癌中erb-b2受体酪氨酸激酶2（ERBB2）的扩增状态对于确定最佳治疗策略至关重要。免疫组织化学（IHC）和荧光原位杂交（FISH）目前分别用于评估蛋白水平和基因拷贝数（CN）。美国联邦药物管理局已批准使用下一代测序（NGS）来测量乳腺癌中的ERBB2 CN作为伴随诊断。然而，CN小于8被评估为“不确定”，这意味着一些被诊断为“HER2阴性”的ERBB2扩增病例可能是假阴性病例。我们回顾了针对乳腺癌（N = 90）和非乳腺癌（N = 19）组织中160个癌症相关基因的基因谱分析结果，并将ERBB2 CN结果与IHC/FISH评分进行了比较。我们通过考虑肿瘤细胞的组织学比例从测量的CN中获得估计的CN，发现ERBB2估计CN为3.2或更高与98.4%（88/90）乳腺癌病例的IHC/FISH联合结果一致，而在非乳腺癌病例中情况并非总是如此。因此，在完成充分的前瞻性临床试验后，NGS估计的ERBB2 CN可被视为抗HER2治疗的诊断测试。
